Abstract

Background

Metabolic and regulatory gene networks generally tend to be stable. However, we have
recently shown that overexpression of the transcriptional activator Hap4p in yeast
causes cells to move to a state characterized by increased respiratory activity. To
understand why overexpression of HAP4 is able to override the signals that normally result in glucose repression of mitochondrial
function, we analyzed in detail the changes that occur in these cells.

Results

Whole-genome expression profiling and fingerprinting of the regulatory activity network
show that HAP4 overexpression provokes changes that also occur during the diauxic shift. Overexpression
of HAP4, however, primarily acts on mitochondrial function and biogenesis. In fact, a number
of nuclear genes encoding mitochondrial proteins are induced to a greater extent than
in cells that have passed through a normal diauxic shift: in addition to genes required
for mitochondrial energy conservation they include genes encoding mitochondrial ribosomal
proteins.

Conclusions

We show that overproduction of a single nuclear transcription factor enables cells
to move to a novel state that displays features typical of, but clearly not identical
to, other derepressed states.